The proposed work will examine interactions among the products of plasma coagulation and fibrinolysis, plasminogen activator (PA) production by vascular intimal cells and peripheral blood mononuclear cells, and procoagulant activity (PCA) elaboration by mononuclear leucocytes. These apparently disparate elements of the potential in vivo hemostatic mechanism have been extensively studied in isolation, but their interactions are poorly understood. Initial objectives will be to extend preliminary observations on suppression and enhancement of both bovine aortic endothelial cell PA and human mononuclear leucocyte PCA by plasma products of coagulation and fibrinolysis. The relationship between altered endothelial cell PA production and production, by the same cell cultures, of a newly identified inhibitor of leucocyte PCA production will also be examined. PA will be assayed in conditioned media and cell extracts of cultured endothelial cells by techniques which identify both fibrin-independent (urokinase-like) and fibrin-dependent PA species. Leucocyte PCA will be assayed in lysates of cultured peripheral blood mononuclear leucocytes. Additional experiments will characterize the extent of proteolytic prothrombin conversion to thrombin required for modulation of endothelial cell PA production, characterize the PA species of peripheral blood monocytes, and examine the effects of products of plasma coagulation upon monocyte PA elaboration. These studies should provide a clearer picture of potential interactions of plasma and cellular components of the in vivo hemostatic mechanism. They are particularly pertinent to our understanding of homostatic events at local vascular sites.